Objective: SYNE1 (Spectrin repeat-containing nuclear envelope protein 1) gene mutation, first diagnosed in French Canadians in 2007, is now reported from many regions around the world. This mutation causes autosomal recessive form of hereditary ataxia. It generaly doesn’t cause polyneuropathy. Pure cerebellar ataxia and additional motor neuron involvement are clinical findings.  Up to now, there were a few case reports from Turkey before.

Background: Not previously defined SYNE1 mutations, detected in two of our patients, were found worthy of study due to their clinical presentations.

Method: Our first patient (54 F, parents are first-degree relatives) applied to our clinic with dysarthria and gait disturbance ongoing for 4 years. There were first order motor neuron signs and cerebellar findings in the examination. The second patient (41 M, parents are first-degree relatives) had pure cerebellar findings. Both cases had distinct cerebellar atrophy in MRGs but second patients’ was more prominent.

Results: In the next generation sequencing conducted in both cases, we have observed mutation on the SYNE1 gene. The first female patient who had more severe findings had a heterozygous mutation, whereas the second case had a homozygous mutation. These mutations were not previously defined in the database.

Conclusion: This case study is striking in several respects. Firstly, it was seen that the SYNE1 mutation could be more prominent in Turkey than it’s already known, and the same mutation could appear with different clinical symptoms in patients. Secondly, the presence of full clinical presentation in a heterozygous mutation signifies that there are more areas unknown to us about the gene. In this study, two cases will be discussed in all aspects.

References: 1- Duan X, Hao Y, Cao Z et al. Autosomal Recessive Cerebellar Ataxia Type 1: Phenotypic and Genetic Correlation in a Cohort of Chinese Patients with SYNE1 Variants. Cerebellum 2021 Feb;20(1):74-82. doi: 10.1007/s12311-020-01186-8.
2- Beaudin M, Matilla-Dueñas A, Soong BW et al. The Classification of Autosomal Recessive Cerebellar Ataxias: a Consensus Statement from the Society for Research on the Cerebellum and Ataxias Task Force. Cerebellum. 2019 Dec;18(6):1098-1125. doi: 10.1007/s12311-019-01052-2.
3- Castillo VJ, Díaz CS, Bustamante ML, Ferreira MG, Teive HAG, Miranda M. Autosomal Recessive Cerebellar Ataxia 1: First Case Report Depicting a Variant in SYNE1 Gene in a Chilean Patient. Cerebellum. 2021 Dec;20(6):938-941. doi: 10.1007/s12311-021-01250-x.
4- Noreau A, Bourassa CV, Szuto A et al. SYNE1 mutations in autosomal recessive cerebellar ataxia. JAMA Neurol. 2013 Oct;70(10):1296-31. doi: 10.1001/jamaneurol.2013.3268.PMID: 23959263.
5- Dupré N, Gros-Louis F, Chrestian N et al. Clinical and genetic study of autosomal recessive cerebellar ataxia type 1. Ann Neurol. 2007 Jul;62(1):93-8. doi: 10.1002/ana.21143.
6- E Yucesan, Sibel A Ugur Iseri, B Bilgic et al. SYNE1 related cerebellar ataxia presents with variable phenotypes in a consanguineous family from Turkey. Neurol Sci 2017 Dec;38(12):2203-2207. doi: 10.1007/s10072-017-3049-8. Epub 2017 Jul 7.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/two-different-clinical-presentations-in-syne1-ataxia-in-turkey/